Gliederung

Background: To determine the relative biological effectiveness (RBE) of carbon ions in the spinal cord and in a prostate tumor of the rat.

Material and methods: The cranial part of the spinal cord of rats was irradiated with 1, 2, 6 or 18 fractions (Fx) of photons or carbon ions (in the plateau or in the middle of a 1 cm spread-out Bragg peak, SOBP), respectively. Biological endpoint was the onset of paresis grade II. In addition, a prostate carcinoma (R3327-AT1) implanted at the hind limb of the rats was irradiated with 1 or 2 Fx of photons or a 2 cm SOBP of carbon ions, respectively. An experiment with 6 Fx is ongoing. Endpoint of these experiments was local tumor control after one year. For all experiments, dose response curves and RBEs were calculated.

Results: For the spinal cord, the RBE-values were 1.44Â±0.08, 1.37Â±0.05, 1.33Â±0.02 and 1.42Â±0.02 for the plateau- and 1.77Â±0.06, 2.17Â±0.06, 2.97Â±0.05, and 5.04Â±0.08 for the peak-irradiations (1, 2, 6, and 18 Fx, respectively). The respective predictions by the local effect model (LEM) were 1.14, 1.19, 1.37, and 1.72 for the plateau- and 1.28, 1.61, 2.35, and 3.80 for the peak irradiations. The measured a/b-values were 2.8Â±0.4 Gy for photons, 2.1Â±0.4 Gy for the plateau and 37.0Â±5.3 Gy for the peak-irradiations, respectively. For the prostate carcinoma, it was shown that local control can be achieved. Three different types of radiation response was seen (see Figure 1 [Fig.Â 1]): i) uncontrolled growth for small doses, ii) temporary reduction of tumor size, followed by continuation of uncontrolled growth, and iii) reduction of tumor size and maintenance of control until the end of follow-up. Preliminary data for 1 and 2 Fx show similarly increased RBEs around 2.3.

Conclusion: Carbon ion irradiations of the spinal cord are significantly more effective in the peak than in the plateau region. A significant fractionation effect was only found for the plateau. The currently applied LEM-version correctly describes the main features although it generally underestimates the RBE in the Bragg-peak by 25%. In the plateau region, overestimations of up to 20% were found at low doses per fraction. The relation to clinical data has to be further analyzed. The investigated tumor model is an anaplastic, hormone-independent tumor. The investigations will be extended to a well differentiated hormone-dependent subline of the same tumor to investigate the impact on RBE. With the established animal models, it is possible to measure RBEs and to investigate the differential RBE between normal and tumor tissues. In this way the therapeutic benefit of high-LET radiation might be experimentally demonstrated as a prove-of-principle.